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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study in compliance with GLP guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: pellets
Details on test material:
The test substance, identified as Eastman TMPD(TM) Glycol Platelets, Batch #: TXARD, was received on June 18, 2012 and was further identified with PSL Reference Number 120618-5D. The test substance was stored at room temperature. Prior to use, the test substance was ground in a coffee mill (Cuisinart, Model DCG-20N). A tissue homogenizer (Tissue Tearor, Biospec, Model 985370) was used to facilitate the preparation of a homogeneous mixture. The ground sample was administered as a 30% w/w mixture in distilled water. Preliminary solubility testing conducted by PSL, indicated that mixtures in excess of 30% (i.e., 40%-80%) were too viscous to be administered properly. Documentation of the methods of synthesis, fabrication, or derivation of the test substance is retained by the Sponsor. The following information related to the characterization of the test substance was provided by the Sponsor:

Composition: 2,2,4-trimethyl-1,3-pentanediol- 99% (CAS# 144-19-4)
Physical Description: White solid (crystals or powder)
Solubility: Soluble in water.
Stability: Test substance was expected to be stable for the duration of testing.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Husbandry

4.A.1 Housing: The animals were singly housed in suspended stainless steel caging with mesh floors, which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 2011 ). Litter paper was placed beneath the cage and was changed at least three times per week.

4.A.2 Animal Room Temperature and Relative Humidity Ranges: 19-23°C and 52-88%, respectively. The humidity was above the targeted upper limit for four days during the study. A portable dehumidifier was used to lower the humidity levels during this time.

4.A.3 Animal Room Air Changes/Hour: 12. Airflow measurements are evaluated regularly and the records are kept on file at Product Safety Labs.

4.A.4 Photoperiod: 12-hour light/dark cycle

4.A.5 Acclimation Period: 9-27 days

4.A.6 Food: Harlan Teklad Global 16% Protein Rodent Diet® #2016. The diet was available ad libitum, except during fasting.

4.A.7 Water: Filtered tap water was supplied ad libitum by an automatic water dispensing system.

4.A.8 Contaminants: There were no known contaminants reasonably expected to be found in the food or water at levels which would have intetfered with the results of this study. Analyses of the food and water are conducted regularly and the records are kept on file at Product Safety Labs.

B. Identification:

4.B.1 Cage: Each cage was identified with a cage card indicating at least the study number, dose level, identification, and sex of the animal.

4.B.2 Animal: A number was allocated to each rat on receipt and a stainless steel ear tag bearing this number was attached to the rat. This number, together with a sequential animal number assigned to study number 34728, constituted unique identification.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled
Details on oral exposure:
A. Selection of Animals
Prior to each dosing, experimentally naive rats (not previously tested) were fasted overnight by removing the feed from their cages. During the fasting period, the rats were examined for health and weighed (initial). Five healthy naive female rats were selected for test.

B. Dose Calculations
Individual doses were calculated based on the initial body weights, taking into account the density (determined by PSL) and concentration of the test mixture.

C. Dosing
The ground test substance was administered as a 30% w/w mixture in distilled water to the stomach using a stainless steel ball-tipped gavage needle attached to an appropriate syringe. Following administration, each animal was returned to its designated cage. Feed was replaced approximately 3-4 hours after dosing.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
A total of 5 individual animals were dosed as follows:

dosing Animal dose level short-term long-term
sequence no. (mg/kg) outcome outcome

1 3101 2000 survival survival
2 3102 2000 survival survival
3 3103 2000 survival survival
4 3104 2000 survival survival
5 3105 2000 survival survival


D. Body Weights
Individual body weights of the animals were recorded prior to test substance administration (initial) and again on Days 7 and 14 (termination) following dosing.

E. Cage-Side Observations
The animals were observed for mortality, signs of gross toxicity, and behavioral changes during the first several hours post-dosing and at least once daily thereafter for 14 days after dosing. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

F. Necropsy
All rats were euthanized via C02 inhalation at the end of the 14-day observation period. Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.

Results and discussion

Preliminary study:
All animals survived test substance administration and gained body weight during the study. Following administration, three animals exhibited ano-genital staining, hypoactivity, reduced fecal volume, hunched posture, gasping, irregular respiration and/or facial staining. However, the animals recovered by Day 3 and along with the remaining two animals were active and healthy for the remainder of the 14-day observation period. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
3 of 5 rats exhibited ano-genital staining, hypoactivity, reduced fecal volume, hunched posture, gasping, irregular respiration and/or facial staining during study days 1-3
Body weight:
INDIVIDUAL BODY WEIGHTS AND DOSES
animal body weight dose vol
no. day 0 day 7 day 14 (mL)
3101 206 228 236 1.4
3102 203 227 230 1.4
3103 168 186 197 1.1
3104 181 206 216 1.2
3105 187 206 215 1.2
Gross pathology:
no abnormalities were noted

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the conditions of this study, the acute oral LD50 of 2,2,4-trimethyl-1,3-pentanediol (TMPD) is greater than 2,000 milligrams per kilogram of body weight in female rats.
Executive summary:

The test substance 2,2,4-trimethyl-1,3-pentanediol (TMPD) was evaluated in an acute oral toxicity test (Up and Down Procedure) in female Sprague Dawley rats. An initial limit dose of 2,000 mg/kg was administered to one healthy female rat by oral gavage. Due to the absence of mortality in this animal, four additional females sequentially received the same dose level. Since these animals survived, no additional animals were tested. Females were selected for the test because they are frequently more sensitive to the toxicity of test compounds than males. All animals were observed for mmiality, signs of gross toxicity, and behavioral changes at least once daily for 14 days after dosing. Body weights were recorded prior to administration and again on Days 7 and 14 (termination) following dosing. Necropsies were performed on all animals at terminal sacrifice. All animals survived test substance administration and gained body weight during the study. Following administration, three animals exhibited ana-genital staining, hypoactivity, reduced fecal volume, hunched posture, gasping, irregular respiration and/or facial staining. However, the animals recovered by Day 3 and along with the remaining two animals were active and healthy. Under the conditions of this study, the acute oral LD50 of 2,2,4-trimethyl-1,3-pentanediol is greater than 2,000 milligrams per kilogram of body weight in female rats.